22-23895034-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002415.2(MIF):​c.282-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,545,856 control chromosomes in the GnomAD database, including 24,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 2463 hom., cov: 33)
Exomes 𝑓: 0.18 ( 22307 hom. )

Consequence

MIF
NM_002415.2 splice_region, intron

Scores

2
Splicing: ADA: 0.0007365
2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.27
Variant links:
Genes affected
MIF (HGNC:7097): (macrophage migration inhibitory factor) This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 22-23895034-C-G is Benign according to our data. Variant chr22-23895034-C-G is described in ClinVar as [Benign]. Clinvar id is 3060033.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MIFNM_002415.2 linkuse as main transcriptc.282-6C>G splice_region_variant, intron_variant ENST00000215754.8 NP_002406.1 P14174I4AY87
MIF-AS1NR_038911.1 linkuse as main transcriptn.868G>C non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MIFENST00000215754.8 linkuse as main transcriptc.282-6C>G splice_region_variant, intron_variant 1 NM_002415.2 ENSP00000215754.7 P14174
ENSG00000251357ENST00000433835.3 linkuse as main transcriptc.605-6C>G splice_region_variant, intron_variant 5 ENSP00000400325.3 H7C1H1

Frequencies

GnomAD3 genomes
AF:
0.175
AC:
26601
AN:
152042
Hom.:
2458
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.143
Gnomad AMI
AF:
0.190
Gnomad AMR
AF:
0.225
Gnomad ASJ
AF:
0.131
Gnomad EAS
AF:
0.196
Gnomad SAS
AF:
0.202
Gnomad FIN
AF:
0.229
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.174
Gnomad OTH
AF:
0.163
GnomAD3 exomes
AF:
0.194
AC:
30212
AN:
155428
Hom.:
3222
AF XY:
0.192
AC XY:
15817
AN XY:
82308
show subpopulations
Gnomad AFR exome
AF:
0.142
Gnomad AMR exome
AF:
0.270
Gnomad ASJ exome
AF:
0.139
Gnomad EAS exome
AF:
0.207
Gnomad SAS exome
AF:
0.199
Gnomad FIN exome
AF:
0.234
Gnomad NFE exome
AF:
0.164
Gnomad OTH exome
AF:
0.189
GnomAD4 exome
AF:
0.176
AC:
245858
AN:
1393700
Hom.:
22307
Cov.:
35
AF XY:
0.177
AC XY:
121390
AN XY:
686648
show subpopulations
Gnomad4 AFR exome
AF:
0.140
Gnomad4 AMR exome
AF:
0.258
Gnomad4 ASJ exome
AF:
0.140
Gnomad4 EAS exome
AF:
0.197
Gnomad4 SAS exome
AF:
0.203
Gnomad4 FIN exome
AF:
0.228
Gnomad4 NFE exome
AF:
0.171
Gnomad4 OTH exome
AF:
0.176
GnomAD4 genome
AF:
0.175
AC:
26628
AN:
152156
Hom.:
2463
Cov.:
33
AF XY:
0.180
AC XY:
13400
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.143
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.131
Gnomad4 EAS
AF:
0.196
Gnomad4 SAS
AF:
0.202
Gnomad4 FIN
AF:
0.229
Gnomad4 NFE
AF:
0.174
Gnomad4 OTH
AF:
0.160
Alfa
AF:
0.134
Hom.:
493
Bravo
AF:
0.171
Asia WGS
AF:
0.217
AC:
755
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MIF-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.6
DANN
Benign
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00074
dbscSNV1_RF
Benign
0.028
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2070766; hg19: chr22-24237221; COSMIC: COSV53158996; API